Study of DNA interactions with steroidal and nonsteroidal estrogen-platinum (II)-based anticancer drugs.
The interactions of the steroidal and nonsteroidal estrogen-platinum (Pt) (II)-based anticancer drugs 16beta-hydroxymethyl-16alpha-[8-(2-pyridin-2-yl-ethylamino)-3,6-dioxaoctyl]-1,3,5(10)-estratrien-3,17betadiol dichloroplatinum (II) (JPM-39), 4-[6-(2'-pyridylethylamino)-butyloxy)-phenyl]-7-methoxy-2,2-dimethyl-3-phenyl-chroman dichloroplatinum (II) (ATG-99), and 1-[(2-aminoethyl)amino]-9,10,10-tris(4-hydroxyphenyl)-9-decene dichloroplatinum (II) (GEB-28) with calf-thymus DNA in vitro using constant DNA concentration and various drug levels were studied. Fourier transform infrared (FTIR) and circular dichroism (CD) were studied with calf-thymus DNA in vitro using constant DNA concentration and various drug levels. FTIR, UV-visible, and CD spectroscopic methods were used to characterize the drug binding mode, the binding constant, and structural variations of DNA in aqueous solution. Spectroscopic evidence showed that the various Pt-based drugs bind indirectly to the major and minor grooves of DNA duplex with some degree of drug-phosphate interaction. The overall binding constants for JPM-39, GEB-28, and ATG-99 are K(JPM-39) = 4.2 (+/-0.75) x 10(3) M(-1), K(GEB-28) = 3.4 (+/-0.65) x 10(3) M(-1), and K(ATG-99) = 2.1 (+/-0.45) x 10(3) M(-1). DNA aggregation occurs at high drug concentration, while DNA remains in the B-family structure.
Froehlich
Emilie
E
Département de Chimie-Biologie, Groupe de Recherche en Biologie Végétale, Université du Québec à Trois-Rivières, Trois-Rivières, Canada.
Gupta
Atul
A
Provencher-Mandeville
Josée
J
Asselin
Eric
E
Bariyanga
Joseph
J
Bérubé
Gervais
G
Tajmir-Riahi
Heidar-Ali
HA
D000970:Antineoplastic Agents / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004967:Estrogens / Q000737:chemistry*; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D010755:Organophosphates / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
D000970:Antineoplastic Agents; D004967:Estrogens; D010755:Organophosphates; D009944:Organoplatinum Compounds; D004247:DNA; C427203:calf thymus DNA